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Mini oral session - Investigational immunotherapy

960MO - Clinical outcomes and immune responses in a phase I/II study of personalized, neoantigen-directed immunotherapy in patients with advanced MSS-CRC, GEA and NSCLC

Date

17 Sep 2021

Session

Mini oral session - Investigational immunotherapy

Topics

Clinical Research;  Immunotherapy

Tumour Site

Oesophageal Cancer;  Gastric Cancer;  Non-Small Cell Lung Cancer;  Colon and Rectal Cancer

Presenters

Daniel Catenacci

Citation

Annals of Oncology (2021) 32 (suppl_5): S829-S866. 10.1016/annonc/annonc705

Authors

D.V. Catenacci1, C. Liao1, S. Maron2, B.J. Solomon3, A. Mahipal4, M.L. Johnson5, D. Carbone6, B.S. Henick7, B. Johnson8, S. Roychowdhury6, K. Mody9, D.H. Ahn10, E. Bournazou11, D. Schenk12, S. Kounlavouth12, L. Kraemer12, G. Talbot13, R. Rousseau13, A.R. Ferguson12, A. Spira14

Author affiliations

  • 1 Medicine, The University of Chicago Medical Centre, 60653 - Chicago/US
  • 2 Medicine, MSKCC - Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 3 Medical Oncology, Peter MacCallum Cancer Center, 8006 - Melbourne/AU
  • 4 Medical Oncology, Mayo Clinic Cancer Center, 55905 - Rochester/US
  • 5 Medical Oncology Department, Sarah Cannon Research Institute-Cancer Centre, 37203 - Nashville/US
  • 6 Medical Oncology, The James Comprehensive Cancer center, Columbus/US
  • 7 Medicine, Columbia University Medical Center College of Physicians & Surgeons - New York Presbyterian Hospital, 10032 - New York/US
  • 8 Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston/US
  • 9 Medical Oncology, Mayo Clinic, 32224 - Jacksonville/US
  • 10 Hematology/medical Oncology, Mayo Clinic Cancer Center, 85054 - Phoenix/US
  • 11 External Innovation And Clinical Collaborations, Bristol-Myers Squibb, 08640 - Lawrenceville/US
  • 12 R&d, Gritstone bio, Inc., 02139 - Cambridge/US
  • 13 R&d, Gritstone bio, Inc., 94608 - Emeryville/US
  • 14 Research Institute, Virginia Cancer Specialist, 22031 - Fairfax/US
More

Resources

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Abstract 960MO

Background

Induction of a strong neoantigen-specific T-cell response may drive tumor lysis and clinical benefit in patients (pts) with poor responses to checkpoint inhibitors (CPI) alone.

Methods

Pts with advanced MSS-CRC (n=10; ≥ 2 lines of therapy), gastroesophageal adenocarcinoma (GEA; n= 10; ≥ 1 line of therapy), and NSCLC (n=2; post-CPI, ≥ 1 line of therapy) were treated with a patient-specific neoantigen-directed heterologous prime/boost vaccine leveraging 20 neoantigens selected using the EDGETM platform plus 30 mg SC ipilimumab and 480 mg IV nivolumab. Prime is a chimpanzee adenovirus (ChAd) and boosts are self-amplifying mRNA formulated in lipid nanoparticles and a second ChAd administration.

Results

22 pts have been treated. Treatment-related AEs and SAEs were mostly Grade 1-2 and reversible with no DLTs. All evaluated pts have a vaccine-induced, neoantigen-specific T-cell response typically evident after priming and further increased or maintained with boosts. Elicited T-cells were specific for multiple neoantigens (including epitope spreading), cytotoxic and infiltrated the tumor. The best response in 18 evaluable pts per RECIST includes 1 confirmed complete response (GEA; > 4 months [mo]), 4 stable disease (1 CRC >18 mo, 1 CRC > 9 mo, 1 CRC and 1 GEA up to 6 mo), 11 progressive disease (PD), and 2 no measurable disease. CD8+ T-cell responses develop over the first 1-3 mo of vaccination and 8 pts progressed within the first 9 weeks, prior to expected treatment effect. Of 9 pts treated beyond RECIST PD, 4 pts did not have confirmed PD at the next scan. In 9 pts with MSS-CRC with at least one scan, 5 were progression-free per iRECIST beyond 6 mo and 4 of the 5 showed circulating tumor DNA (ctDNA) response (decrease ≥ 50% from baseline) indicating clinical activity in MSS-CRC. Enrollment continues; data will be updated.

Conclusions

Neoantigen-directed prime/boost immunotherapy in combination with CPI is well-tolerated and generates strong and persistent T-cells to multiple neoantigens. Increases in T-cells correlate with a novel pattern of response and clinical benefit characterized by a transient spike then decline in ctDNA, tumor markers, and tumor size, notably in pts with MSS-CRC.

Clinical trial identification

NCT03639714.

Editorial acknowledgement

Legal entity responsible for the study

Gritstone bio, Inc.

Funding

Gritstone bio, Inc.

Disclosure

D.V. Catenacci: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Five Prime Therapeutics; Financial Interests, Personal, Advisory Board: Genentech/Roche; Financial Interests, Personal, Advisory Board: Gritstone Oncology; Financial Interests, Personal, Advisory Board: Guardant Health; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Taiho Pharmaceutical; Financial Interests, Personal, Advisory Board: Tempus; Financial Interests, Personal, Speaker’s Bureau: Foundation Medicine; Financial Interests, Personal, Speaker’s Bureau: Genentech; Financial Interests, Personal, Speaker’s Bureau: Guardant Health; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Speaker’s Bureau: Tempus. C. Liao: Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board: Lexicon; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: QED; Financial Interests, Personal, Advisory Board: Transthera Therapeutics; Financial Interests, Personal, Advisory Board: Blueprint Medicine; Financial Interests, Personal, Advisory Board: Genentech. S. Maron: Financial Interests, Personal, Advisory Board: Basilea; Financial Interests, Personal, Advisory Board: Daiichi-Sar; Financial Interests, Personal, Advisory Board: Natera; Financial Interests, Personal, Stocks/Shares: Calithera; Non-Financial Interests, Institutional, Other: Guardant; Financial Interests, Institutional, Other: Genentech. B.J. Solomon: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Genentech/Roche; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Royalties: Veristrat (Biodesix); Financial Interests, Personal, Royalties: UpToDate. A. Mahipal: Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Research Grant: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Karyopharm; Financial Interests, Institutional, Research Grant: Novartis. M.L. Johnson: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Otsuka; Financial Interests, Institutional, Research Grant: Abbvie; Financial Interests, Institutional, Research Grant: Acerta Pharma; Financial Interests, Institutional, Research Grant: Adaptimmune; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Apexigen; Financial Interests, Institutional, Research Grant: Arcus; Financial Interests, Institutional, Research Grant: Array; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Atreca; Financial Interests, Institutional, Research Grant: BeiGene; Financial Interests, Institutional, Research Grant: Birdie; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Checkpoint Therapeutics; Financial Interests, Institutional, Research Grant: Corvus; Financial Interests, Institutional, Research Grant: CytomX; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Dynavax; Financial Interests, Institutional, Research Grant: EMD Serono; Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Institutional, Research Grant: Genocea; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: Gritstone Oncology; Financial Interests, Institutional, Research Grant: Guardant; Financial Interests, Institutional, Research Grant: Hengrui; Financial Interests, Institutional, Research Grant: Immunocore; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Jounce; Financial Interests, Institutional, Research Grant: Kadmon; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Loxo; Financial Interests, Institutional, Research Grant: Lycera; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Mirati; Financial Interests, Institutional, Research Grant: Neovia; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: OncoMed; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Regeneron; Financial Interests, Institutional, Research Grant: Ribon; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Shattuck Labs; Financial Interests, Institutional, Research Grant: Stem CentRx; Financial Interests, Institutional, Research Grant: Syndax; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Tarveda Therapeutics; Financial Interests, Institutional, Research Grant: TCR2 Therapeutics; Financial Interests, Institutional, Research Grant: University of Michigan; Financial Interests, Institutional, Research Grant: WindMIL. D. Carbone: Financial Interests, Institutional, Research Grant: Gritstone bio, Inc.; Financial Interests, Personal, Research Grant: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Abbvie; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Biocept; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Board: Foundation Medicine; Financial Interests, Personal, Advisory Board: Genentech/Roche; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Guardant Health; Financial Interests, Personal, Advisory Board: Helsinn; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Inivata; Financial Interests, Personal, Advisory Board: Inovio; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis Oncology; Financial Interests, Personal, Advisory Board: Peregrine Pharmaceuticals; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Synta; Financial Interests, Personal, Advisory Board: Loxo; Financial Interests, Personal, Research Grant: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Nexus. B. Johnson: Financial Interests, Personal, Advisory Board: Gritstone bio, Inc.; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Taiho Oncology; Financial Interests, Personal, Research Grant: Bristol-Myers Squibb; Financial Interests, Personal, Research Grant: Syntrix. S. Roychowdhury: Financial Interests, Institutional, Stocks/Shares: Johnson&Johnson; Financial Interests, Personal, Advisory Board: Abbvie; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: QED Therapeutics; Financial Interests, Personal, Research Grant: Ignyta; Financial Interests, Personal, Research Grant: Incyte; Financial Interests, Personal, Research Grant: QED Therapeutics; Financial Interests, Personal, Research Grant: Takeda. K. Mody: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Genentech/Roche; Financial Interests, Personal, Advisory Board: Merrimack; Financial Interests, Personal, Advisory Board: Vicus Therapeutics; Financial Interests, Personal, Research Grant: Agios; Financial Interests, Personal, Research Grant: Ariad; Financial Interests, Personal, Research Grant: ArQule; Financial Interests, Personal, Research Grant: FibroGen; Financial Interests, Personal, Research Grant: MedImmune; Financial Interests, Personal, Research Grant: Senhwa Biosciences; Financial Interests, Personal, Research Grant: Taiho Pharmaceutical; Financial Interests, Personal, Research Grant: TRACON Pharma; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Gritstone Oncology; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Basilea; Financial Interests, Personal, Stocks/Shares: CytoDyn; Financial Interests, Personal, Stocks/Shares: Oncotherapeutics. E. Bournazou: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. D. Schenk: Financial Interests, Personal, Full or part-time Employment: Gritstone bio, Inc. S. Kounlavouth: Financial Interests, Personal, Full or part-time Employment: Gritstone bio, Inc. L. Kraemer: Financial Interests, Personal, Full or part-time Employment: Gritstone bio, Inc. G. Talbot: Financial Interests, Personal, Full or part-time Employment: Gritstone bio, Inc. R. Rousseau: Financial Interests, Personal, Full or part-time Employment: Gritstone bio, Inc.; Financial Interests, Personal, Stocks/Shares: Gritstone bio, Inc. A.R. Ferguson: Financial Interests, Personal, Full or part-time Employment: Gritstone bio, Inc.; Financial Interests, Personal, Stocks/Shares: Gritstone bio, Inc. All other authors have declared no conflicts of interest.

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